There has been an alarming increase in abuse of prescription opioids in recent years. Data from the 2002 National Survey on Drug Use and Health, for example, indicate that abuse of prescription opioids increased by more than 400% between 1990 and 2000. This increase in prescription opioid abuse has been associated with increases in drug-related crime, numerous adverse health consequences and treatment demand. Despite these statistics, we know of no published studies evaluating treatments for prescription opioid abuse. This proposal is submitted in response to NIDA's PA 04-110 "Prescription Drug Abuse" and outlines two experimental studies designed to programmatically evaluate a combined behavioral-pharmacological treatment for prescription opioid abuse. The platform behavioral treatment delivered to patients in both studies is the Community Reinforcement Approach (CRA), an efficacious therapy for promoting healthy lifestyle changes in licit and illicit drug abusers. The pharmacological treatments will be a buprenorphine detoxification followed by a regimen of naltrexone therapy. In Study 1 we propose a parametric investigation to determine an effective buprenorphine dose-tapering schedule that prevents the poor retention and high relapse rates that often undermine detoxification programs. In Study 2 we propose a parametric investigation to determine an effective regimen of naltrexone therapy that can sustain opioid abstinence following the buprenorphine detoxification. The overarching goal of this proposal is to develop a manualized, efficacious treatment for prescription opioid abuse. The two randomized clinical trials proposed in this application have the potential to contribute important new scientific and clinical knowledge critical to the development of effective interventions for prescription opioid abuse. The aims of the project are also directly relevant to NIDA's mission of developing effective, empirically-based treatments for drug dependence. Finally, the proposed research holds significant potential for impacting the status of public health in general. Development of efficacious treatments for this emerging population will help to reduce the vast economic and societal costs associated with prescription opioid abuse.